The package inserts for all Schedule IV stimulant medications carry boxed warnings indicating risk of abuse potential and/or risk of psychological dependence. Additionally, boxed warnings for certain stimulant medications (methylphenidate and dexmethylphenidate products) indicate risk of psychotic episodes. Other stimulant medications (amphetamine, dextroamphetamine, lisdexamfetamine dimesylate, methamphetamine, and mixed salts of amphetamine products) carry boxed warnings alerting clinicians that misuse of these medications may cause serious cardiovascular adverse events, including sudden death.
Bupropion is a stimulating antidepressant with a primarily dopaminergic and noradrenergic mechanism of action. (Refer to Table 2 in the PDQ summary on Depression for more information.) Preliminary evidence from a small open-label study (n = 21) suggests that the sustained release (SR) form of bupropion has potential as an effective therapeutic agent for treating CRF with or without comorbid depressive symptoms.[Level of evidence: II] Seizure, a rare but serious side effect of this agent, did not occur in this study (the maximum dose of bupropion SR used in this study was 300 mg).
Table 2. Centrally Acting Stimulants for Adult Cancer Patients
AUC = area under the curve; MAOI = monoamine oxidase inhibitor; SSRI = selective serotonin reuptake inhibitor.
|Drug||Dosage||Comments/Primary Side Effects|
|Dextroamphetamine (Dexedrine)||2.5 mg/d (start)||Schedule II. Major potential interactions with citalopram and venlafaxine.|
|5-30 mg/d in 2 to 3 divided doses|
|Methylphenidate (Ritalin)||2.5 mg/d (start)||Schedule II. High-fat meals may increase AUC. Peak concentration 102 hours after ingestion. Do not use with MAOIs as it can precipitate hypertensive crisis. Antidepressants that increase norepinephrine can cause increased amphetamine side effects. Concomitant use with SSRI can result in increased SSRI concentrations.|
|Titrate up to 54 mg/d (27 mg D-isomer)|
|Modafinil (Provigil)||50-100 mg (start)||Schedule IV. Avoid driving/operation of machinery until effects are known. Do not take at bedtime. Peak concentration in 2-4 hours. Food slows absorption by about 1 hour but does not affect bioavailability. Decreases efficacy of birth control pills.|
|100-200 mg every morning|
|Armodafinil (Nuvigil)||50 mg (start)||Schedule IV. Avoid driving/operation of machinery until effects are known. Do not take at bedtime. Peak concentration in 2 hours if fasting, slowed to as many as 4 hours if fed, but food does not affect bioavailability. Decreases efficacy of birth control pills.|
|25-250 mg every morning|
On the basis of limited clinical experience and acknowledging a lack of evidence in randomized controlled trials, it might be reasonable to consider a psychostimulant such as methylphenidate or modafinil for the treatment of severe fatigue, particularly for short periods of time (a couple of weeks) in patients with advanced disease. When the use of these medications is being considered, it is important to obtain informed consent, with careful discussion of risks, benefits, and alternatives. Continuous monitoring of cardiovascular parameters is crucial when these medications are used, especially in patients with preexisting cardiovascular issues and in patients being treated with known cardiotoxic chemotherapeutic regimens (e.g., anthracyclines). In certain cases, consulting with cardiology services might be necessary. Longer-term psychostimulant therapy is not advisable at this time because there is limited information about its potential negative effects and longer-term benefits.